tbuckley/cabot-search huggingface dataset:
Demographic Characteristics Associated With Perceptions of Personal Utility in Genetic and Genomic Testing
Authors: Emily G. Miller, Jennifer L. Young, Anoushka Rao, Eliana Ward-Lev, Meghan C. Halley
Journal: JAMA Network Open (2023)

Importance The expansion of genetic and genomic testing in health care has led to recognition that these tests provide personal as well as clinical utility to patients and families. However, available systematic reviews on this topic have not reported the demographic backgrounds of participants in studies of personal utility, leaving generalizability unclear. Objective To determine the demographic characteristics of participants in studies examining the personal utility of genetic and genomic testing in health care. Evidence Review For this systematic review, we utilized and updated the results of a highly cited 2017 systematic review on the personal utility of genetics and genomics, which identified relevant articles published between January 1, 2003, and August 4, 2016. We also used the original methods to update this bibliography with literature published subsequently up to January 1, 2022. Studies were screened for eligibility by 2 independent reviewers. Eligible studies reported empirical data on the perspectives of patients, family members, and/or the general public in the US on the personal utility of any type of health-related genetic or genomic test. We utilized a standardized codebook to extract study and participant characteristics. We summarized demographic characteristics descriptively across all studies and by subgroup based on study and participant characteristics. Findings We included 52 studies with 13 251 eligible participants. Sex or gender was the most frequently reported demographic characteristic (48 studies [92.3%]), followed by race and ethnicity (40 studies [76.9%]), education (38 studies [73.1%]), and income (26 studies [50.0%]). Across studies, participants disproportionately were women or female (mean [SD], 70.8% [20.5%]), were White (mean [SD], 76.1% [22.0%]), had a college degree or higher (mean [SD], 64.5% [19.9%]), and reported income above the US median (mean [SD], 67.4% [19.2%]). Examination of subgroups of results by study and participant characteristics evidenced only small shifts in demographic characteristics. Conclusions and Relevance This systematic review examined the demographic characteristics of individual participants in studies of the personal utility of health-related genetic and genomic testing in the US. The results suggest that participants in these studies were disproportionately White, college-educated women with above-average income. Understanding the perspectives of more diverse individuals regarding the personal utility of genetic and genomic testing may inform barriers to research recruitment and uptake of clinical testing in currently underrepresented populations.
Frontal Hypoperfusion and Cerebellar Hyperperfusion in Transient Alcoholic Cerebellar Degeneration
Authors: Tzyy-Ling Chuang, Yuh-Feng Wang
Journal: Clinical Nuclear Medicine (2023)

A 55-year-old man consumed approximately 10 units of alcohol daily for 25 years, developing social withdrawal after retiring. For 2 months, he walked diagonally to the right, with a right shoulder droop. He spoke and walked slowly, but his speech was clear. After 20 days of abstinence, his symptoms improved, and his walk became more steady. Brain MRI revealed no specific finding. Brain perfusion scintigraphy with 99m Tc-ECD on 2-tailed view display in eZIS showed hypoperfusion in the prefrontal, frontal, and left anterior temporal lobes and left thalamus and hyperperfusion in the posterior white matter, parietal-occipital cortical regions, pons, and cerebellum.
Comparing the Detection Performance Between Multiparametric Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen PET/CT in Patients With Localized Prostate Cancer
Authors: Yuh-Feng Wang, Chun-Yu Lo, Li-Yu Chen, Chi-Wei Chang, Ya-Ting Huang, Ya-Yao Huang, Yi-Hsiu Huang
Journal: Clinical Nuclear Medicine (2023)

Purpose Multiparametric MRI (mpMRI) has been promoted as an auxiliary diagnostic tool for prostate biopsy. However, prostate-specific membrane antigen (PSMA) including 68 Ga-PSMA-11, 18 F-DCFPyL, and 18 F-PSMA-1007 applied PET/CT imaging was an emerging diagnostic tool in prostate cancer patients for staging or posttreatment follow-up, even early detecting. Many studies have used PSMA PET for comparison with mpMRI to test the diagnostic ability for early prostate cancer. Unfortunately, these studies have shown conflicting results. This meta-analysis aimed to compare the differences in diagnostic performance between PSMA PET and mpMRI for detecting and T staging localized prostatic tumors. Methods This meta-analysis involved a systematic literature search of PubMed/MEDLINE and Cochrane Library databases. The pooling sensitivity and specificity of PSMA and mpMRI verified by pathological analysis were calculated and used to compare the differences between the 2 imaging tools. Results Overall, 39 studies were included (3630 patients in total) from 2016 to 2022 in the current meta-analysis and found that the pooling sensitivity values for localized prostatic tumors and T staging T3a and T3b of PSMA PET were 0.84 (95% confidence interval [CI], 0.83–0.86), 0.61 (95% CI, 0.39–0.79), and 0.62 (95% CI, 0.46–0.76), respectively, whereas those of mpMRI were found to be 0.84 (95% 0.78–0.89), 0.67 (95% CI, 0.52–0.80), and 0.60 (95% CI, 0.45–0.73), respectively, without significant differences ( P &gt; 0.05). However, in a subgroup analysis of radiotracer, the pooling sensitivity of 18 F-DCFPyL PET was higher than mpMRI (relative risk, 1.10; 95% CI, 1.03–1.17; P &lt; 0.01). Conclusions This meta-analysis found that whereas 18 F-DCFPyL PET was superior to mpMRI at detecting localized prostatic tumors, the detection performance of PSMA PET for localized prostatic tumors and T staging was comparable to that of mpMRI.
67Ga-PSMA I&amp;T for Radioguided Surgery of Lymph Node Metastases in Patients With Biochemical Recurrence of Prostate Cancer
Authors: Thomas Winkens, Frank Peter Berger, Susan Foller, Julia Greiser, Sebastian Groeber, Marc-Oliver Grimm, Martin Freesmeyer, Christian Kuehnel
Journal: Clinical Nuclear Medicine (2023)

Purpose Radioguided lymph node dissection in patients with prostate cancer, and suffering from biochemical recurrence has been described thoroughly during the past few years. Several prostate-specific membrane antigen (PSMA)–directed ligands labeled with 111 In, 99m Tc, and 68 Ga have been published; however, limitations regarding availability, short half-life, high costs, and unfavorable high energy might restrict frequent use. This study aims at introducing 67 Ga as a promising radionuclide for radioguided surgery. Methods Retrospective analysis was performed on 6 patients with 7 PSMA-positive lymph node metastases. 67 Ga-PSMA I&amp;T (imaging and therapy) was synthesized in-house and intravenously applied according to §13 2b of the German Medicinal Products Act. Radioguided surgery was performed 24 hours after injection of 67 Ga-PSMA I&amp;T using a gamma probe. Patient urine samples were collected. Occupational and waste dosimetry was performed to describe hazards arising from radiation. Results 67 Ga-PSMA application was tolerated without adverse effects. Five of 7 lymph nodes were detected on 22-hour SPECT/CT in 4 of 6 patients. During surgery, all 7 lymph node metastases were identified by positive gamma probe signal. Relevant accumulation of 67 Ga was observed in lymph node metastases (32.1 ± 15.1 kBq). Histology analysis of near-field lymph node dissection revealed more lymph node metastases than PET/CT (and gamma probe measurements) identified. Waste produced during inpatient stay required decay time of up to 11 days before reaching exemption limits according to German regulations. Conclusions Radioguided surgery using 67 Ga-PSMA I&amp;T is a safe and feasible option for patients suffering from biochemical recurrence of prostate cancer. 67 Ga-PSMA I&amp;T was successfully synthesized according to Good Manufacturing Practice guidelines. Radioguided surgery with 67 Ga-PSMA I&amp;T does not lead to relevant radiation burden to urology surgeons and represents a novel interdisciplinary approach in nuclear medicine and urology.
Correlations and Timeliness of COVID-19 Surveillance Data Sources and Indicators ― United States, October 1, 2020–March 22, 2023
Authors: Heather M. Scobie, Mark Panaggio, Alison M. Binder, Molly E. Gallagher, William M. Duck, Philip Graff, Benjamin J. Silk
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

When the U.S. COVID-19 public health emergency declaration expires on May 11, 2023, national reporting of certain categories of COVID-19 public health surveillance data will be transitioned to other data sources or will be discontinued; COVID-19 hospitalization data will be the only data source available at the county level (1). In anticipation of the transition, national COVID-19 surveillance data sources and indicators were evaluated for purposes of ongoing monitoring. The timeliness and correlations among surveillance indicators were analyzed to assess the usefulness of COVID-19-associated hospital admission rates as a primary indicator for monitoring COVID-19 trends, as well as the suitability of other replacement data sources. During April 2022-March 2023, COVID-19 hospital admission rates from the National Healthcare Safety Network (NHSN)† lagged 1 day behind case rates and 4 days behind percentages of positive test results and COVID-19 emergency department (ED) visits from the National Syndromic Surveillance Program (NSSP). In the same analysis, National Vital Statistics System (NVSS) trends in the percentage of deaths that were COVID-19-associated, which is tracked by date of death rather than by report date, were observable 13 days earlier than those from aggregate death count data, which will be discontinued (1). During October 2020-March 2023, strong correlations were observed between NVSS and aggregate death data (0.78) and between the percentage of positive SARS-CoV-2 test results from the National Respiratory and Enteric Viruses Surveillance System (NREVSS) and COVID-19 electronic laboratory reporting (CELR) (0.79), which will also be discontinued (1). Weekly COVID-19 Community Levels (CCLs) will be replaced with levels of COVID-19 hospital admission rates (low, medium, or high) which demonstrated >99% concordance by county during February 2022-March 2023. COVID-19-associated hospital admission levels are a suitable primary metric for monitoring COVID-19 trends, the percentage of COVID-19 deaths is a timely disease severity indicator, and the percentages of positive SARS-CoV-2 test results from NREVSS and ED visits serve as early indicators for COVID-19 monitoring. Collectively, these surveillance data sources and indicators can support monitoring of the impact of COVID-19 and related prevention and control strategies as ongoing public health priorities.
Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy
Authors: David Simmons, Jincy Immanuel, William M Hague, Helena Teede, Christopher J Nolan, Michael J Peek, Jeff R Flack, Mark McLean, Vincent Wong, Emily Hibbert, Alexandra Kautzky-Willer, Jürgen Harreiter, Helena Backman, Emily Gianatti, Arianne Sweeting, Viswanathan Mohan, Joanne Enticott, N Wah Cheung
Journal: New England Journal of Medicine (2023)

Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. Download a PDF of the Research Summary. We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, −5.6 percentage points; 95% confidence interval [CI], −10.1 to −1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, −1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, −0.04 kg; 95% CI, −0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.) QUICK TAKE VIDEO SUMMARYTreating Gestational Diabetes Early in Pregnancy 02:12
Early versus Second-Trimester Screening and Treatment for Diabetes in Pregnancy
Authors: Michael F. Greene
Journal: New England Journal of Medicine (2023)

After a decades-long debate regarding the usefulness of universal screening for and treatment of gestational diabetes mellitus, two large randomized, controlled trials of screening in the second trimester that were published in the Journal in 20051 and 20092 clearly showed that such screening and treatment reduced morbidity related to gestational diabetes, when diagnosed, among both mothers and their offspring. Universal second-trimester screening for gestational diabetes has long been recommended by the American College of Obstetricians and Gynecologists and the American Diabetes Association. Many of the complications associated with untreated gestational diabetes, such as excessive fetal growth, birth injury, preeclampsia, and . . .
Profiling the Somatic Mutational Landscape of Breast Tumors from Hispanic/Latina Women Reveals Conserved and Unique Characteristics
Authors: Yuan Chun Ding, Hanbing Song, Aaron W. Adamson, Daniel Schmolze, Donglei Hu, Scott Huntsman, Linda Steele, Carmina S. Patrick, Shu Tao, Natalie Hernandez, Charleen D. Adams, Laura Fejerman, Kevin Gardner, Anna María Nápoles, Eliseo J. Pérez-Stable, Jeffrey N. Weitzel, Henrik Bengtsson, Franklin W. Huang, Susan L. Neuhausen, Elad Ziv
Journal: Cancer Research (2023)

Abstract Somatic mutational profiling is increasingly being used to identify potential targets for breast cancer. However, limited tumor-sequencing data from Hispanic/Latinas (H/L) are available to guide treatment. To address this gap, we performed whole-exome sequencing (WES) and RNA sequencing on 146 tumors and WES of matched germline DNA from 140 H/L women in California. Tumor intrinsic subtype, somatic mutations, copy-number alterations, and expression profiles of the tumors were characterized and compared with data from tumors of non-Hispanic White (White) women in The Cancer Genome Atlas (TCGA). Eight genes were significantly mutated in the H/L tumors including PIK3CA, TP53, GATA3, MAP3K1, CDH1, CBFB, PTEN, and RUNX1; the prevalence of mutations in these genes was similar to that observed in White women in TCGA. Four previously reported Catalogue of Somatic Mutations in Cancer (COSMIC) mutation signatures (1, 2, 3, 13) were found in the H/L dataset, along with signature 16 that has not been previously reported in other breast cancer datasets. Recurrent amplifications were observed in breast cancer drivers including MYC, FGFR1, CCND1, and ERBB2, as well as a recurrent amplification in 17q11.2 associated with high KIAA0100 gene expression that has been implicated in breast cancer aggressiveness. In conclusion, this study identified a higher prevalence of COSMIC signature 16 and a recurrent copy-number amplification affecting expression of KIAA0100 in breast tumors from H/L compared with White women. These results highlight the necessity of studying underrepresented populations. Significance: Comprehensive characterization of genomic and transcriptomic alterations in breast tumors from Hispanic/Latina patients reveals distinct genetic alterations and signatures, demonstrating the importance of inclusive studies to ensure equitable care for patients. See related commentary by Schmit et al., p. 2443
Object-centered population coding in CA1 of the hippocampus
Authors: Anne Nagelhus, Sebastian O. Andersson, Soledad Gonzalo Cogno, Edvard I. Moser, May-Britt Moser
Journal: Neuron (2023)

Objects and landmarks are crucial for guiding navigation and must be integrated into the cognitive map of space. Studies of object coding in the hippocampus have primarily focused on activity of single cells. Here, we record simultaneously from large numbers of hippocampal CA1 neurons to determine how the presence of a salient object in the environment alters single-neuron and neural-population activity of the area. The majority of the cells showed some change in their spatial firing patterns when the object was introduced. At the neural-population level, these changes were systematically organized according to the animal's distance from the object. This organization was widely distributed across the cell sample, suggesting that some features of cognitive maps-including object representation-are best understood as emergent properties of neural populations.
TGFβ Antagonizes IFNγ-Mediated Adaptive Immune Evasion via Activation of the AKT–Smad3–SHP1 Axis in Lung Adenocarcinoma
Authors: Fan Ye, Zihao Cai, Boyu Wang, Chenxi Zeng, Yu Xi, Shaojie Hu, Rirong Qu, Zhiwei Yuan, Jiaqi Yue, Yitao Tian, Xue Wang, Xiangning Fu, Lequn Li
Journal: Cancer Research (2023)

IFNγ-mediated signaling in tumor cells can induce immunosuppressive responses and cause tumor resistance to immunotherapy. Blocking TGFβ promotes T lymphocyte infiltration and turns immunologically cold tumors into hot tumors, thereby improving the efficacy of immunotherapy. Several studies have shown that TGFβ inhibits IFNγ signaling in immune cells. We thus sought to determine whether TGFβ affects IFNγ signaling in tumor cells and plays a role in the development of acquired resistance to immunotherapy. TGFβ stimulation of tumor cells increased SHP1 phosphatase activity in an AKT-Smad3-dependent manner, decreased IFNγ-mediated tyrosine phosphorylation of JAK1/2 and STAT1, and suppressed the expression of STAT1-dependent immune evasion-related molecules, e.g., PD-L1, IDO1, herpes virus entry mediator (HVEM), and galectin-9 (Gal-9). In a lung cancer mouse model, dual blockade of TGFβ and PD-L1 led to superior antitumor activity and prolonged survival compared with anti-PD-L1 therapy alone. However, prolonged combined treatment resulted in tumor resistance to immunotherapy and increased expression of PD-L1, IDO1, HVEM, and Gal-9. Interestingly, after initial anti-PD-L1 monotherapy, dual TGFβ and PD-L1 blockade promoted both immune evasion gene expression and tumor growth compared with that in tumors treated with continuous PD-L1 monotherapy. Alternatively, treatment with JAK1/2 inhibitor following initial anti-PD-L1 therapy effectively suppressed tumor growth and downregulated immune evasion gene expression in tumors, indicating the involvement of IFNγ signaling in immunotherapy resistance development. These results demonstrate an unappreciated effect of TGFβ on the development of IFNγ-mediated tumor resistance to immunotherapy.Blocking TGFβ facilitates IFNγ-mediated resistance to anti-PD-L1 therapy due to the role of TGFβ in inhibiting IFNγ-induced immunoevasion by increasing SHP1 phosphatase activity in tumor cells.
Age-dependent immune and lymphatic responses after spinal cord injury
Authors: Andrea Francesca M. Salvador, Taitea Dykstra, Justin Rustenhoven, Wenqing Gao, Susan M. Blackburn, Kesshni Bhasiin, Michael Q. Dong, Rafaela Mano Guimarães, Sriharsha Gonuguntla, Igor Smirnov, Jonathan Kipnis, Jasmin Herz
Journal: Neuron (2023)
One-session treatment is as effective as multi-session therapy for young people with phobias
Authors: Helen Saul, Brendan Deeney, Jemma Kwint, Lina Gega
Journal: BMJ (2023)

The studyWright B, Tindall L, Scott AJ, et al. One-session treatment compared with multisession CBT in children aged 7-16 years with specific phobias: the ASPECT non-inferiority RCT. Health Technol Assess 2022;26:1-174.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/one-session-cbt-treatment-effective-for-young-people-with-phobias/.
Androgen receptor blockade resistance with enzalutamide in prostate cancer results in immunosuppressive alterations in the tumor immune microenvironment
Authors: Pengfei Xu, Joy C Yang, Bo Chen, Christopher Nip, Jonathan E Van Dyke, Xiong Zhang, Hong-Wu Chen, Christopher P Evans, William J Murphy, Chengfei Liu
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Emerging data suggest that patients with enzalutamide-treated prostate cancer with increased programmed death-ligand 1 (PD-L1) expression may benefit from anti-PD-L1 treatment. Unfortunately, the Phase III IMbassador250 clinical trial revealed that the combination of atezolizumab (a PD-L1 inhibitor) and enzalutamide failed to extend overall survival in patients with castration-resistant prostate cancer (CRPC). However, the mechanisms underlying treatment failure remain unknown. Methods Human CRPC C4-2B cells and murine Myc-CaP cells were chronically exposed to increasing concentrations of enzalutamide and the cells resistant to enzalutamide were referred to as C4-2B MDVR and Myc-CaP MDVR, respectively. The mechanisms of action in drug-resistant prostate cancer cells were determined using RNA sequencing analyses, RNA interference, real-time PCR, western blotting, and co-culturing technologies. Myc-CaP and Myc-CaP MDVR tumors were established in syngeneic FVB mice, and tumor-infiltrating leukocytes were isolated after enzalutamide treatment. The stained immune cells were determined by flow cytometry, and the data were analyzed using FlowJo. Results Immune-related signaling pathways (interferon alpha/gamma response, inflammatory response, and cell chemotaxis) were suppressed in human enzalutamide-resistant prostate cancer cells. PD-L1 was overexpressed and negatively regulated by androgen receptor signaling in resistant cells and patient with CRPC cohorts. Enzalutamide treatment decreased CD8 + T-cell numbers but increased monocytic myeloid-derived suppressor cell (M-MDSC) populations and PD-L1 expression within murine Myc-CaP tumors. Similarly, chemotaxis and immune response-regulating signaling pathways were suppressed, and PD-L1 expression was also increased using enzalutamide-resistant Myc-CaP MDVR cells. Notably, MDSC populations were significantly increased in Myc-CaP MDVR orthotopic tumors compared with those in Myc-CaP parental tumors. Co-culturing bone marrow cells with Myc-CaP MDVR cells significantly promoted MDSC differentiation and shifted towards M2 macrophage skewing. Conclusions Our study suggests that immunosuppressive signaling can be promoted directly by enzalutamide-resistant prostate cancer cells and may be a potential means by which the efficacy of immune checkpoint inhibitors in enzalutamide-resistant prostate cancer is diminished.